2-methyl-[4,6-di-O-acetyl-1,2-di-deoxy-3-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyrano]-[2,1,d]-2-oxazoline | 69659-49-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-methyl-[4,6-di-O-acetyl-1,2-di-deoxy-3-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyrano]-[2,1,d]-2-oxazoline
• 英文别名: O¹-((3aR)-6t-acetoxy-5c-acetoxymethyl-2-methyl-(3ar,7ac)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7c-yl)-O²,O³,O⁴-triacetyl-β-D-glucopyranuronic acid methyl ester；methyl (2S,3S,4S,5R,6R)-6-[[(3aR,5R,6S,7R,7aR)-6-acetyloxy-5-(acetyloxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-7-yl]oxy]-3,4,5-triacetyloxyoxane-2-carboxylate
• CAS: 69659-49-0
• 化学式: C₂₅H₃₃NO₁₆
• 分子量: 603.534
• InChiKey: KBDYYWVMOZAPHH-PSUXIWLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  42
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  207
• 氢给体数：
  0
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  2-methyl-[4,6-di-O-acetyl-1,2-di-deoxy-3-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyrano]-[2,1,d]-2-oxazoline 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 (2S,3S,4S,5R,6R)-3,4,5-Trihydroxy-6-((3aR,5R,6S,7R,7aR)-6-hydroxy-5-hydroxymethyl-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7-yloxy)-tetrahydro-pyran-2-carboxylic acid methyl ester
  参考文献：
  名称：

  酶促合成人工透明质酸：一种使用过渡态类似物单体合成糖胺聚糖的新方法。

  摘要：

  DOI：

  10.1021/ja017104+
• 作为产物：
  描述：

  (methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)-(1->3)-2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranose 在 硫酸 、 乙酸酐 、 溶剂黄146 作用下， 生成 2-methyl-[4,6-di-O-acetyl-1,2-di-deoxy-3-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-α-D-glucopyrano]-[2,1,d]-2-oxazoline
  参考文献：
  名称：

  P1- [2-乙酰氨基-2-脱氧-3-O-（β-D-吡喃葡萄糖基尿酸）-α-D-吡喃葡萄糖基] P2-二苯甲酰基二磷酸酯的合成

  摘要：

  摘要从2-乙酰氨基-4,6-二-O-乙酰基-2-脱氧-3-O-（2,3,4-三-O-乙酰基-β-D-吡喃葡萄糖基尿酸酯）-α-D-葡萄糖吡喃糖（20）是通过常规反应顺序制备的结晶中间体，可以实现N-乙酰基-透明二磺酰基尿嘧啶二聚体二磷酸的全合成。关键步骤之一涉及将二糖20转化为甲基恶唑啉26，然后再以约30％的产率将其转化为稳定的结晶性二糖磷酸衍生物。甲基ox唑啉26由相应的甲基α-糖苷通过乙酰水解直接制备。类似地，烯丙基α-糖苷被转化为26。

  DOI：

  10.1016/s0008-6215(00)83783-0

文献信息

• Hyaluronic Acid Oligosaccharide Derivatives Alleviate Lipopolysaccharide-Induced Inflammation in ATDC5 Cells by Multiple Mechanisms
  作者：Hesuyuan Huang、Xuyang Ding、Dan Xing、Jianjing Lin、Zhongtang Li、Jianhao Lin

  DOI：10.3390/molecules27175619

  日期：——

  High molecular weight hyaluronic acids (HMW-HAs) have been used for the palliative treatment of osteoarthritis (OA) for decades, but the pharmacological activity of HA fragments has not been fully explored due to the limited availability of structurally defined HA fragments. In this study, we synthesized a series glycosides of oligosaccharides of HA (o-HAs), hereinafter collectively referred to as o-HA derivatives. Their effects on OA progression were examined in a chondrocyte inflammatory model established by the lipopolysaccharide (LPS)-challenged ATDC5 cells. Cell Counting Kit-8 (CCK-8) assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showed that o-HA derivatives (≤100 μg/mL) exhibited no cytotoxicity and pro-inflammatory effects. We found that the o-HA and o-HA derivatives alleviated LPS-induced inflammation, apoptosis, autophagy and proliferation-inhibition of ATDC5 cells, similar to the activities of HMW-HAs. Moreover, Western blot analysis showed that different HA derivatives selectively reversed the effects of LPS on the expression of extracellular matrix (ECM)-related proteins (MMP13, COL2A1 and Aggrecan) in ATDC5 cells. Our study suggested that o-HA derivatives may alleviate LPS-induced chondrocyte injury by reducing the inflammatory response, maintaining cell proliferation, inhibiting apoptosis and autophagy, and decreasing ECM degradation, supporting a potential oligosaccharides-mediated therapy for OA.

  高分子量透明质酸（HMW-HAs）已经用于缓解骨关节炎（OA）的治疗几十年了，但由于结构定义的透明质酸片段的可用性有限，透明质酸片段的药理活性尚未完全探索。在本研究中，我们合成了一系列透明质酸寡糖的糖苷，统称为o-HA衍生物。我们检查了它们对ATDC5细胞中脂多糖（LPS）挑战建立的软骨细胞炎症模型中OA进展的影响。细胞计数试剂盒-8（CCK-8）试验和逆转录定量聚合酶链反应（RT-qPCR）表明，o-HA衍生物（≤100 μg/mL）没有细胞毒性和促炎症作用。我们发现，o-HA和o-HA衍生物减轻了LPS诱导的ATDC5细胞炎症、凋亡、自噬和增殖抑制，类似于HMW-HAs的活性。此外，Western blot分析显示，不同的HA衍生物选择性地逆转了LPS对ATDC5细胞外细胞基质（ECM）相关蛋白（MMP13、COL2A1和AggrECan）表达的影响。我们的研究表明，o-HA衍生物可能通过减少炎症反应、维持细胞增殖、抑制凋亡和自噬、降低ECM降解来减轻LPS诱导的软骨细胞损伤，支持一种潜在的寡糖介导的OA治疗方法。